Previous work in this laboratory has demonstrated that there is a streptococcal extracellular protein which is secreted primarily by those streptococcal strains isolated directly from patients with acute post-streptococcal nephritis (APSGN). This protein of 46,000 daltons appears to be antigenically identical in all strains tested and antibody to this purified protein is found in the biopsy material of patients with APSGN. Present work has shown that streptococcal antigen(s) appear to be present in circulating immune complexes isolated from patients with post-streptococcal sequelae and that there is an antigen(s) within the complex which is unique to nephritic immune complexes. Secondly the sera of APSGN patients contain an antibody which reacts uniquely with a protein of 46,000 daltons present only in the extracellular products of nephritis associated strains. Finally, cellular studies in APSGN patients have demonstrated that they have a depressed response to streptococcal antigens during the acute phase which persists for long periods of time after cessation of the disease. Our proposed studies will concentrate on the following areas: 1) further purification and study of this protein and its biological properties; 2) determination of the relationships of the antigen and antibody in the immune complex and the antibody in the human sera to an antigen of 46,000 daltons; 3) prospective studies in the Trinidad population on the levels and significance of this antibody in a population where APSGN is both endemic and epidemic; 4) exploration of the cellular mechanism involved in the suppressed response to streptococcal antigens in these patients. The overall objective of this project will be to determine whether or not patients with nephritis have an antibody to our "nephritogenic" protein and whether this antibody is protective in the general population. A corollary objective will be to pursue our cellular studies to determine whether the suppressed response to streptococcal antigens might be a factor leading to chronicity of disease.